Search

Background: High-dose therapy and autologous stem cell transplantation (ASCT) is often considered for older patients (age >60 years) with relapsed/refractory aggressive lymphomas. Although registry data support the safety and potential efficacy of this approach, there are no prospective trials evaluating outcomes of ASCT in older patients. We evaluated the result of second-line chemotherapy and ASCT in older versus younger patients in the CCTG randomized LY.12 trial., Patients and Methods: From August 2003 to November 2011, 619 patients with relapsed/refractory aggressive lymphoma were randomized to gemcitabine, dexamethasone, cisplatin (GDP) or dexamethasone, cytarabine, cisplatin (DHAP); 177 patients (28.6%) enrolled were >60.0 years of age (range, 60-74) and 442 were ≤60.0 years of age. After two to three cycles, responding patients proceeded to ASCT. Intention-to-treat analysis was used to compare response rate, transplantation rate, event-free survival (EFS) and overall survival (OS) between patients aged ≤60.0 and >60.0 years., Results: Patient characteristics were comparable between the two cohorts, except a larger proportion of older patients had high International Prognostic Index risk scores. Response to salvage therapy was 48.6% for patients aged  >60.0 versus 43.0% for those aged  ≤60.0 (P = 0.21). Transplantation rates were also similar: 50.3% versus 49.8% (P = 0.87) for older versus younger patients. Rates of febrile neutropenia and adverse events requiring hospitalization were comparable for older and younger patients (30.5% versus 22.9% and 37.9% versus 32.1%, respectively). With a median follow-up of 53 months, there was no difference in 4-year OS (36% and 40% for patients aged >60.0 and ≤60.0 years, P = 0.42), or 4-year EFS (20% versus 28%, P = 0.43). Mortality from salvage therapy was 8/174 (4.60%) and 5/436 (1.15%), and 100-day mortality post-ASCT was 7/88 (8.06%) and 4/219 (1.85%)., Conclusion: This subgroup analysis suggests that older patients derive similar benefit from salvage therapy and ASCT to younger patients, with acceptable toxicity., Clinicaltrials.gov Identifier: NCT00078949., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (<12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

Numerous studies have reported the feasibility and safety of autologous SCT (ASCT) in patients with multiple myeloma (MM) and mild to moderate renal impairment, but there are limited data in dialysis-dependent patients. In this retrospective study, we reviewed the toxicities and efficacy outcomes of 33  MM patients with dialysis-dependent renal failure who underwent ASCT at our institution from 1998 to 2012. The most common grade 3 non-hematologic toxicities were mucositis (49%), infection (15%) and bleeding (6%). Atrial dysrhythmias (24%) and delirium (30%) of all grades were also common. Hematologic toxicities included febrile neutropenia (88%); and RBC and platelet transfusions were required by 71 and 100% of patients, respectively. Transplant-related mortality (TRM) was high at 15%, predominantly caused by septic shock. Response to ASCT was at least VGPR (very good PR) in 50%, PR in 46.2% and stable disease (SD) in 3.8%. Median OS was 5.6 years, comparable to our overall institutional data. Overall, seven patients became dialysis independent. We conclude that ASCT can be an effective treatment for dialysis-dependent MM patients, with high response rates and survival. However, toxicities and a high TRM are observed indicating that further studies are needed to enhance the safety of this approach.

The role of a second autologous stem cell transplant (ASCT) as salvage therapy is unclear, particularly with the availability of novel agents to treat progressive multiple myeloma (MM). We retrospectively reviewed all MM patients who received a second ASCT as salvage therapy at our center from March 1992 to December 2009. Eighty-one MM patients received a second ASCT for relapsed MM. The median time to relapse after first transplant was 39 months (9.83-100). All patients received reinduction therapy before the second ASCT. The high-dose regimen given before the second ASCT consisted of melphalan (MEL) alone in the majority. Complete response, very good partial response, and partial response were seen in 7.7%, 39.7%, and 50%, respectively, at day 100 post-ASCT; the median time to relapse after the second ASCT was 19 months. Early deaths occurred in 2.6%. Median progression-free survival (PFS) based on the time to myeloma relapse after first ASCT was 9.83 months (relapse ≤ 24 months) and 17.3 months (relapse ≥ 24 months) (P < .05). Median overall survival (OS) was 28.47 months (relapse ≤ 24 months) and 71.3 months (relapse >24 months) (P = .006). Second ASCT is a feasible and safe option for salvage therapy in MM. The best outcome was observed in patients whose time to progression was >24 months after first ASCT, as these patients had a subsequent PFS lasting over 1 year and an OS of almost 6 years., (Copyright © 2012. Published by Elsevier Inc.)

High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve excellent clinical responses in patients with POEMS syndrome (Jimenez Zepeda et al., Blood 2010;116:2403; Gertz et al., Am J Hematol 2005;79:319-328; Gherardi et al., Ann Neurol 1994;35:501-505; Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Salem et al., J Immunol 2009;182:2030-2040; Salem et al., Cancer Immunol Immunother 2010;59:341-353; Salem et al., Cell Immunol 2010;261:134-143). However, High-dose melphalan with ASCT should be considered carefully due to its treatment-related morbidity (Vuckovic et al., Blood 2003;101:2314-2317), especially in patients with poor performance status owing to polyneuropathy and multiorgan involvement, such as cardiac, respiratory, and renal failure. Significant increases in the concentration of circulating macrophage colony-stimulating factor, erythropoietin, IL-6, and TNF-α, reach near maximal values at approximately day +12, predating neutrophil engraftment, and clinically manifest with fever, rash and edema (Dispenzieri et al., Eur J Haematol 2008;80:397-406). Depending on the definition used, approximately 50% of patients satisfied criteria for engraftment syndrome (ES) (Vuckovic et al., Blood 2003;101:2314-2317). ES occurs in 27-47% of patients who undergo ASCT; mortality rate is reported from 8% to 18% (Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Vuckovic et al., Blood 2003;101:2314-2317). We have therefore reviewed our experience with ASCT in patients with POEMS syndrome who were treated with cyclophosphamide and prednisone as induction therapy followed by cyclophosphamide mobilization with an emphasis on treatment-related morbidity and frequency of ES. Our study confirms that ASCT is a feasible and efficacious treatment for patients with POEMS syndrome. In addition, the use of CP followed by cyclophosphamide mobilization decreases the incidence of PES leading to less morbidity and mortality rates., (2011 Wiley-Liss, Inc.)